Clinical significance of TC21 overexpression in oral cancer

Muzafar A. MacHa, Ajay Matta, Uma Sriram, Alok Thakkar, N. K. Shukla, Siddhartha Datta Gupta, Ranju Ralhan

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

Background: In search of novel molecular markers for oral cancer, we reported increased levels of TC21/R-Ras2 transcripts in oral squamous cell carcinoma by differential display. The aim of this study was to determine the clinical significance of TC21 in oral cancer. Methods: Immunohistochemical analysis of TC21 protein expression was carried out in 120 leukoplakias, 83 OSCCs and 30 non-malignant tissues, confirmed by immunoblotting, and correlated with clinicopathological parameters as well as disease prognosis. Co-immunoprecipitation assays were carried out to identify the interaction partners of TC21 protein in oral cancer cells and tissues. Results: TC21 nuclear expression increased from normal oral tissues to leukoplakia and frank malignancy (P < 0.001). TC21 overexpression was observed in 74.2% leukoplakia with no dysplasia, 75.9% dysplasias and 79.5% OSCCs in comparison with normal oral tissues. Receiver operating characteristic analysis showed that the area-under-the curve values were 0.895, 0.885, and 0.919, while the positive predictive values were 95.8%, 95.6%, and 97.1%, for nuclear immunostaining for normal versus leukoplakia with no dysplasia, leukoplakic lesions with dysplasia, and OSCCs, respectively. Immunoblotting confirmed overexpression of TC21 in oral lesions. Using co-immunoprecipitation assays, we showed interactions of TC21 with Erk2, PI3-K, 14-3-3ζ and 14-3-3σ proteins in oral cancer cells. Conclusion: Our findings suggested that alteration in TC21 expression is an early event in oral cancer and correlates with poor prognosis of OSCCs. TC21 interactions with Erk2, PI3-K, 14-3-3ζ and 14-3-3σ proteins in oral cancer cells and tissues suggests the involvement of TC21 in signaling pathways in oral cancer.

Original languageEnglish (US)
Pages (from-to)477-485
Number of pages9
JournalJournal of Oral Pathology and Medicine
Volume39
Issue number6
DOIs
StatePublished - Jul 2010

Keywords

  • R-Ras2
  • TC21
  • dysplasia
  • leukoplakia
  • oral squamous cell carcinoma

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Oral Surgery
  • Otorhinolaryngology
  • Cancer Research
  • Periodontics

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  • Cite this

    MacHa, M. A., Matta, A., Sriram, U., Thakkar, A., Shukla, N. K., Datta Gupta, S., & Ralhan, R. (2010). Clinical significance of TC21 overexpression in oral cancer. Journal of Oral Pathology and Medicine, 39(6), 477-485. https://doi.org/10.1111/j.1600-0714.2009.00854.x